Accelerated Atherosclerosis in Patients with Systemic Lupus Erythematosus and the Role of Selected Adipocytokines in This Process

Systemic lupus erythematosus (SLE) can affect various systems and organs. The most severe forms of the disease affect the kidneys, the central nervous system, and the heart. Cardiac and cardiovascular system diseases are inter alia caused by atherosclerosis, vasculitis, and thromboembolic events. Patients with SLE are at a higher risk of developing accelerated atherosclerosis. This process in SLE patients cannot be explained solely based on classical risk factors. Recently, some adipocytokines/adipokines have been indicated in the development of atherosclerosis, inflammation, and immune processes. It has also been postulated that adipokines might regulate the immune response and hence the atherogenic process. In this work, the factors contributing to accelerated atherosclerosis in SLE patients with special respect to vasculitis/vascular injury are presented, and selected adipocytokines, that is leptin, resistin, and adiponectin, with their relation to atherosclerosis and SLE, are under discussion

Wpływ wieku biologicznego na czynność komórek progenitorowych śródbłonka

Aging in relation to organism biology is a gradual loss of restoration potential. Biological age is a subject of interest in many fields as genetics, nephrology and oncology. Endothelial progenitor cells (EPCs) are responsible for regeneration of endothelium. The dysfunction of EPCs, which seems to be the consequence of the aging process, may lead to the development of cardiovascular disorders. EPCs disturbances may reduce EPCs number, impair the migration ability and clonogenic potential of EPCs. This paper presents some aspects of aging process of EPCs according to the latest reports concerning the biological age. It contains the description of biological age conception. Moreover it shows the chosen markers of biological age (telomeres, proteins regulating cell cycle, proteases) and modulating factors like administered medications and ingested chemical compounds. Some therapeutic actions which may interfere in biological age are also presented. Kardiol Pol 2010; 68, supl. V: 405-411Starzenie według biologii organizmu polega na stopniowej utracie jego potencjału regeneracyjnego. Wiek biologiczny stanowi przedmiot zainteresowania wielu nauk, takich jak genetyka, nefrologia czy onkologia. Komórki progenitorowe śródbłonka (EPCs) odpowiadają za regenerację endotelium. Istotnym ogniwem rozwoju chorób układu sercowo-naczyniowego jest dysfunkcja EPCs, która wydaje się konsekwencją starzenia biologicznego. Polega ona na zmiejszeniu liczby, zdolności do migracji oraz osłabieniu potencjału różnicowania EPCs. Celem artykułu jest scharakteryzowanie niektórych istotnych aspektów starzenia komórek progenitorowych śródbłonka na podstawie doniesień na temat wieku biologicznego. Artykuł definiuje założenia wieku biologicznego. Ponadto przedstawia charakterystykę wybranych markerów wieku biologicznego (telomerów, białek regulujących cykl komórkowy, proteaz) oraz czynników go modulujących, takich jak stosowane leki czy spożywane związki chemiczne. Szczególny nacisk położono na przedstawienie tych działań lekarskich, które powodują ingerencję w wiek biologiczny EPCs. Kardiol Pol 2010; 68, supl. V: 405-41

Assessment of selected B cells populations in the workers of X-ray departments

Objectives: Workers of X-ray departments are occupationally exposed to long-term low levels of ionizing radiation (LLIR), which may affect their humoral immunity. The aim of the study was to assess the influence of LLIR on the number and proportion of B cells (CD19+), B1 cells (CD5+CD19+) and memory B cells (CD27+CD19+) in peripheral blood of such workers. Materials and Methods: In the study group of 47 X-ray departments workers and the control group consisting of 38 persons, the number and percentage of CD19+, CD5+CD19+, CD27+CD19+ cells as well as CD5+CD19+/CD19+ and CD27+CD19+/CD19+ cell ratios were assessed using flow cytometry. Additionally, the study group was divided into 2 groups by the length of employment below and over 15 years and analysis adjusted for age and smoking habit was performed. Results: The total number of CD19+ cells showed significant increase in the group of workers in comparison with the persons from the control group, whereas the percentage of CD5+CD19+ cells as well as CD27+CD19+/CD19+ and CD5+CD19+/CD19+ cell ratios were lower. Percentage, number of CD5+CD19+ cells and CD5+CD19+/CD19+ cell ratio were significantly lower in the workers with length of employment longer than 15 years in comparison with those employed below 15 years. Moreover, we found positive associations between the number of CD19+ cells and employment as well as smoking habit, whereas the number of CD5+CD19+ cells was positively associated with cigarette smoking alone. Percentage of CD5+CD19+ cells as well as CD5+CD19+/CD19+ and CD27+CD19+/CD19+ cell ratios were negatively correlated with employment. Conclusions: The study suggests association between the suppressive influence of low level ionizing radiation on circulating in peripheral blood, especially of B1 cells as well as of memory B cells, in workers of X-ray units, which is adverse in relation to microbiological threat

Reduction of serum IGF-I levels in patients affected with Monoclonal Gammopathies of undetermined significance or Multiple Myeloma. Comparison with bFGF, VEGF and K-ras gene mutation

<p>Abstract</p> <p>Background</p> <p>Serum levels of IGF-I in patients affected with multiple myeloma (MM) have been scarcely studied. The present study is aimed to explore this point comparing 55 healthy subjects, 71 monoclonal gammopaties of uncertain significance (MGUS) and 77 overt MM patients. In the same subjects, basic FGF and VEGF, have been detected. All three mediators were analyzed in function of K-<it>ras </it>mutation and melphalan response. Concerning IGF-I, two representative monitoring examples have also been added.</p> <p>Methods</p> <p>Cytokine determinations were performed by commercially available ELISA kits, while K12-<it>ras </it>mutation was investigated on genomic DNA isolated from bone marrow cell specimens by RFLP-PCR assay.</p> <p>Results</p> <p>Significant reductions of IGF-I levels were observed in MGUS and MM as compared with healthy controls. In addition, MM subjects showed significantly decreased serum IGF-I levels than MGUS. Conversely, increasing levels were observed for bFGF and VEGF, molecules significantly correlated. A multivariate analysis corrected for age and gender confirmed the significant difference only for IGF-I values (P = 0.01). K12-<it>ras </it>mutation was significantly associated with malignancy, response to therapy and with significantly increased serum bFGF levels.</p> <p>Conclusion</p> <p>IGF-I reduction in the transition: Controls→MGUS→MM and changes observed over time suggest that IGF-I should be furtherly studied in future clinical trials as a possible monitoring marker for MM.</p

Exhausted Cytotoxic Control of Epstein-Barr Virus in Human Lupus

Systemic Lupus Erythematosus (SLE) pathology has long been associated with an increased Epstein-Barr Virus (EBV) seropositivity, viremia and cross-reactive serum antibodies specific for both virus and self. It has therefore been postulated that EBV triggers SLE immunopathology, although the mechanism remains elusive. Here, we investigate whether frequent peaks of EBV viral load in SLE patients are a consequence of dysfunctional anti-EBV CD8+ T cell responses. Both inactive and active SLE patients (n = 76 and 42, respectively), have significantly elevated EBV viral loads (P = 0.003 and 0.002, respectively) compared to age- and sex-matched healthy controls (n = 29). Interestingly, less EBV-specific CD8+ T cells are able to secrete multiple cytokines (IFN-γ, TNF-α, IL-2 and MIP-1β) in inactive and active SLE patients compared to controls (P = 0.0003 and 0.0084, respectively). Moreover, EBV-specific CD8+ T cells are also less cytotoxic in SLE patients than in controls (CD107a expression: P = 0.0009, Granzyme B release: P = 0.0001). Importantly, cytomegalovirus (CMV)-specific responses were not found significantly altered in SLE patients. Furthermore, we demonstrate that EBV-specific CD8+ T cell impairment is a consequence of their Programmed Death 1 (PD-1) receptor up-regulation, as blocking this pathway reverses the dysfunctional phenotype. Finally, prospective monitoring of lupus patients revealed that disease flares precede EBV reactivation. In conclusion, EBV-specific CD8+ T cell responses in SLE patients are functionally impaired, but EBV reactivation appears to be an aggravating consequence rather than a cause of SLE immunopathology. We therefore propose that autoimmune B cell activation during flares drives frequent EBV reactivation, which contributes in a vicious circle to the perpetuation of immune activation in SLE patients

TNF-α and TGF-β Counter-Regulate PD-L1 Expression on Monocytes in Systemic Lupus Erythematosus

Monocytes in patients with systemic lupus erythematosus (SLE) are hyperstimulatory for T lymphocytes. We previously found that the normal program for expression of a negative costimulatory molecule programmed death ligand-1 (PD-L1) is defective in SLE patients with active disease. Here, we investigated the mechanism for PD-L1 dysregulation on lupus monocytes. We found that PD-L1 expression on cultured SLE monocytes correlated with TNF-α expression. Exogenous TNF-α restored PD-L1 expression on lupus monocytes. Conversely, TGF-β inversely correlated with PD-L1 in SLE and suppressed expression of PD-L1 on healthy monocytes. Therefore, PD-L1 expression in monocytes is regulated by opposing actions of TNF-α and TGF-β. As PD-L1 functions to fine tune lymphocyte activation, dysregulation of cytokines resulting in reduced expression could lead to loss of peripheral T cell tolerance

Cytomegalovirus infection in pediatric rheumatic diseases: a review

Human cytomegalovirus (HCMV) is familiar to pediatric rheumatologists mainly as a cause of opportunistic disease in pharmacologically immune suppressed patients. However, HCMV also has a variety of immuno-modulatory effects, through which it may influence the course of rheumatic conditions. In this article we discuss the interplay between HCMV and the immune system, and review the clinical manifestations, diagnosis, and treatment of HCMV infection in children with rheumatic disease